Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks
Background: Next-Generation Sequencing (NGS) methods specifically Whole-Exome Sequencing (WES) have demonstrated promising findings with a high accuracy of 91%-99% in Pharmacogenomics (PGx). A PGx-based panel can be utilized to minimize adverse drug reactions (ADRs) and maximize the treatment effica...
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Shiraz University of Medical Sciences
2025-02-01
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| Series: | Iranian Journal of Medical Sciences |
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| Online Access: | https://ijms.sums.ac.ir/article_50438_08d496e83abcf5314728148bca1bcbab.pdf |
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| author | Alireza Sharafshah Majid Motovali-Bashi Parvaneh Keshavarz |
| author_facet | Alireza Sharafshah Majid Motovali-Bashi Parvaneh Keshavarz |
| author_sort | Alireza Sharafshah |
| collection | DOAJ |
| description | Background: Next-Generation Sequencing (NGS) methods specifically Whole-Exome Sequencing (WES) have demonstrated promising findings with a high accuracy of 91%-99% in Pharmacogenomics (PGx). A PGx-based panel can be utilized to minimize adverse drug reactions (ADRs) and maximize the treatment efficacy. Remarkably, Cancer Pain Management (CPM) is a cutting-edge concept in modern medicine. Thus, this study aimed to investigate the WES results by a PGx-based panel containing genes involved in Pain, Anti-inflammatory, and Immunomodulating agents (PAIma) signaling pathways. Methods: A total of 200 unrelated Iranians (100 western and 100 northern) were included. 100 WES results were analyzed through the PAIma panel. After DNA extraction, 100 samples were genotyped by Multiplex-Amplification-Refractory Mutation System (ARMS) PCR. A primary in silico investigation performed on 128 candidate genes through Protein-Protein Interactions (PPIs) and Gene-miRNA Interactions (GMIs) via the STRING database, and miRTargetLink2, respectively. Additionally, Enrichment Analysis (EA) was applied to find the unknown interplays among these three major pathways by Enrichr. Results: 55,590 annotations through 21 curated pathways were filtered, 900 variants were found, and 128 genes were refined. Finally, 54 candidate variants (48 non-synonymous single nucleotide variants (nsSNVs), 2 stop-gained, 1 frameshift, and 3 splicing) remained. Conclusion: Conclusively, six potentially actionable variants including rs1695 (GSTP1), rs628031 (SLC22A1), rs17863778 (UGT1A7), rs16947 (CYP2D6), rs2257401 (CYP3A7), and rs2515641 (CYP2E1) had the most deviations among Iranians, compared with the reference genome, which should be genotyped for drug prescribing. Remarkably, PPIs, GMIs, and EA revealed potential risks of carcinogenesis and cancer phenotypes resulting from PAIma pathways genes. |
| format | Article |
| id | doaj-art-e9bb8967d89e482295bf534e3d21072f |
| institution | DOAJ |
| issn | 0253-0716 1735-3688 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Shiraz University of Medical Sciences |
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| series | Iranian Journal of Medical Sciences |
| spelling | doaj-art-e9bb8967d89e482295bf534e3d21072f2025-08-20T03:00:32ZengShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-07161735-36882025-02-015029811110.30476/ijms.2024.101852.345050438Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer RisksAlireza Sharafshah0Majid Motovali-Bashi1Parvaneh Keshavarz2Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranDivision of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranCellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, IranBackground: Next-Generation Sequencing (NGS) methods specifically Whole-Exome Sequencing (WES) have demonstrated promising findings with a high accuracy of 91%-99% in Pharmacogenomics (PGx). A PGx-based panel can be utilized to minimize adverse drug reactions (ADRs) and maximize the treatment efficacy. Remarkably, Cancer Pain Management (CPM) is a cutting-edge concept in modern medicine. Thus, this study aimed to investigate the WES results by a PGx-based panel containing genes involved in Pain, Anti-inflammatory, and Immunomodulating agents (PAIma) signaling pathways. Methods: A total of 200 unrelated Iranians (100 western and 100 northern) were included. 100 WES results were analyzed through the PAIma panel. After DNA extraction, 100 samples were genotyped by Multiplex-Amplification-Refractory Mutation System (ARMS) PCR. A primary in silico investigation performed on 128 candidate genes through Protein-Protein Interactions (PPIs) and Gene-miRNA Interactions (GMIs) via the STRING database, and miRTargetLink2, respectively. Additionally, Enrichment Analysis (EA) was applied to find the unknown interplays among these three major pathways by Enrichr. Results: 55,590 annotations through 21 curated pathways were filtered, 900 variants were found, and 128 genes were refined. Finally, 54 candidate variants (48 non-synonymous single nucleotide variants (nsSNVs), 2 stop-gained, 1 frameshift, and 3 splicing) remained. Conclusion: Conclusively, six potentially actionable variants including rs1695 (GSTP1), rs628031 (SLC22A1), rs17863778 (UGT1A7), rs16947 (CYP2D6), rs2257401 (CYP3A7), and rs2515641 (CYP2E1) had the most deviations among Iranians, compared with the reference genome, which should be genotyped for drug prescribing. Remarkably, PPIs, GMIs, and EA revealed potential risks of carcinogenesis and cancer phenotypes resulting from PAIma pathways genes.https://ijms.sums.ac.ir/article_50438_08d496e83abcf5314728148bca1bcbab.pdfpharmacogenomicswhole exome sequencinggenetic variationcancer |
| spellingShingle | Alireza Sharafshah Majid Motovali-Bashi Parvaneh Keshavarz Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks Iranian Journal of Medical Sciences pharmacogenomics whole exome sequencing genetic variation cancer |
| title | Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks |
| title_full | Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks |
| title_fullStr | Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks |
| title_full_unstemmed | Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks |
| title_short | Pharmacogenomics-Based Detection of Variants Involved in Pain, Anti-inflammatory and Immunomodulating Agents Pathways by Whole Exome Sequencing and Deep in Silico Investigations Revealed Novel Chemical Carcinogenesis and Cancer Risks |
| title_sort | pharmacogenomics based detection of variants involved in pain anti inflammatory and immunomodulating agents pathways by whole exome sequencing and deep in silico investigations revealed novel chemical carcinogenesis and cancer risks |
| topic | pharmacogenomics whole exome sequencing genetic variation cancer |
| url | https://ijms.sums.ac.ir/article_50438_08d496e83abcf5314728148bca1bcbab.pdf |
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